Nebulization of Liposomes. III. The Effects of Operating Conditions and Local Environment

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Abstract
Multilamellar liposomes (MLV) of saturated phosphatidylcholine and dipalmitoyl phosphatidylglycerol (DPPG) (9:1 mole ratio) containing 5,6-carboxyfluorescein (CF) were prepared and extruded through 1.0-µm polycarbonate membranes. Diluted aqueous dispersions were aerosolized for a total of 80 min using a Collison nebulizer under a variety of conditions. The effects of air pressure, temperature, buffer osmotic strength, and pH on nebulized liposome dispersions were studied. Changes in air pressure produced large changes in the percentage release of CF and ranged from 1.3% (4 psig) to 88.2% (50 psig) after 80 min of nebulization. The temperature of the nebulizer dispersions dropped during experiments. The extent of the temperature drop varied according to the air pressure used and ranged from 5°C (4 psig) to 11°C (≥30 psig). The temperature of dispersions caused no increase in CF release until the gel-to-liquid crystalline transition temperature was exceeded (54.6°C), whereupon a 20% increase in leakage was observed after 80 min of nebulization. Aerosol mass output was relatively unaffected by the starting temperature of experiments when conducted within the ambient temperature range. Leakage from the liposomes was increased in hypotonic solution but decreased in hypertonic solutions. At a buffer pH of 2.85 the percentage leakage of CF was increased ≈18% compared to that at pH 7.2 and pH 10.75. Results show that the stability of liposomes composed of saturated phosphatidylcholine and DPPG (9:1 mole ratio) is affected by the operating and environmental conditions under which aerosolization takes place, with air pressure having the greatest effect.

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